The Bcl-2 Protein: a Prognostic Indicator Strongly Related to p53 Protein in Lymph Node-Negative Breast Cancer Patients

Abstract

The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohis-tochemical procedures in hormonally regulated epithelia. We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([ ³ H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [ ³ H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [ ³ H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [ ³ H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [ ³ H]thy-midine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multi-variate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [ ³ H]thymidine-labeling index was still statistically significant as a predictor for both events. The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression. [J Natl Cancer Inst 86: 499–504, 1994]